Approche endophénotypique des comportements addictifs

The prevalence of tobacco, cannabis and alcohol dependences is considered as high in most countries, having devastating psychological, social and physical consequences. These disorders are supported by social, cultural, psychological and biological factors. Their clinical presentation is also complex, suggesting an important phenotypic and genetic heterogeneity. Family studies as well as twin studies suggest a high heritability of these disorders, ranging between 30% and 60%. However, very few genetic variants have been considered as formerly associated with addictions. The phenotypic and clinical heterogeneity could contribute at least in part to the lack of positive results in genetic studies. In the present dissertation, we will show how the disentanglement of these disorders constitute a new approach, allowing to discover novel phenotypes, more homogeneous and with a stronger genetic support. Our first work will examine the association between some variant along the dopamine transporter gene and complication associated with alcohol dependence, namely alcohol withdrawal seizures. Then we will show how the age at onset of alcohol dependence constitutes a novel phenotype of interest. We will also consider the association of tobacco smoking in alcohol dependent participants as an intermediate phenotype. Finally, we will consider the subjective effect of cannabis during the first use as a new endophenotype for cannabis dependence.